1. Field of the Invention
The present invention relates generally to the administration of drugs and drug therapy and more particularly to the introduction of drugs into the lungs.
2. Description of the Prior Art
Patients entering the hospital with pulmonary afflictions serious enough to require invasive treatment are generally subject to two types of procedure: 1) long-term ventilation, where the patient's breathing is augmented by air forced through an endotracheal tube inserted into the trachea, and 2) short-term (usually one day) treatment with a bronchoscope, a small fiber-optic device which is inserted directly into the trachea, enabling the physician to view specific areas of the upper respiratory tract, as well as individual bronchi and lobes of the lung. Patients requiring these treatments also generally require simultaneous administration of therapeutic substances directly to the lungs. In the case of the ventilated patient, drug administration is effected by the introduction of an aerosol of nebulized medicament into the ventilator air stream, a procedure with a notoriously variable, low efficiency (0-30%; typically 5-10%) of drug delivery in most hospital settings. In the case of the bronchoscopy procedure, substances can be administered in liquid form through the working channel of the bronchoscope, a small (1.2-2.2 mm diameter) opening, open at both ends, which traverses the length of the bronchoscope. For patients requiring pulmonary drug administration without either ventilation or visualization, a simple endotracheal tube is inserted into the trachea and the drug is delivered in liquid form, using an ordinary syringe.
Similar considerations apply to the administration of solutions of pulmonary test substances to experimental animals. Dosing with liquid to anesthetized subjects is either done directly, by inserting a small delivery tube into the trachea, or by first inserting a larger endotracheal tube, through which the liquid is then delivered. Delivery of significant amounts of inhaled aerosols to conscious experimental animals is even more problematic than aerosol delivery to anesthetized human subjects, owing to the fact that most small mammals are obligate nose breathers.
In general, then, while liquid delivery is fast, simple and inexpensive, distribution in the lung is uneven at best, with little alveolar involvement except if large volumes are administered, in which case the subject can suffer considerable respiratory distress. Further, the process can be a wasteful one, since much of the liquid bolus may be cleared, coughed up, and swallowed or expectorated. Nebulizer-generated aerosol delivery, on the other hand, while promoting a more uniform distribution of the delivered material in the lung, is slow, complicated and expensive. Because of the low and variable efficiency of delivery, dose quantification is difficult.
Recently, a promising alternative to these two modes of pulmonary drug delivery has emerged, termed "intratracheal aerosolization", which methodology involves the generation of a fine aerosol at the tip of a long, relatively thin tube which is suitable for insertion into the trachea, such as is illustrated in my prior U.S. Pat. Nos. 5,579,758; 5,594,987; and 5,606,789, which are each incorporated by reference herein. It is now well established that intratracheal aerosolization can be a highly effective alternative to liquid instillation and aerosol inhalation for the testing of pharmaceuticals in experimental animals. For example, radiograms of Technicium.sup.99 -labelled DNA-lipid complex administered to rats in this way have shown very deep and broad penetration into all lobes of the lungs. In another approach, intratracheal aerosolization of compounds which disrupt lung tissues (e.g., endotoxin, neutrophil elastase) has been shown to be 41/2-5 times as effective as liquid instillation of these materials. In these and many similar applications, intratracheal aerosolization has proven to be a highly efficient, fast, and relatively inexpensive mode of pulmonary drug delivery. In addition, the effectiveness of this device in studies with experimental animals suggests its possible application to human subjects.
The present invention has been developed in view of the foregoing and discloses another pulmonary drug delivery device.